product monograph apo-propranolol usp beta-adrenergic

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PRODUCT MONOGRAPH

PrAPO-PROPRANOLOL

(Propranolol Hydrochloride)

(10, 20, 40, 80 and 120 mg Tablets)

USP

Beta-Adrenergic Receptor Blocking Agent

APO TEX INC.,

Toronto, Ontario

M9L 1T9

DATE OF REVISION:

29 January 2021

Control Number: 242932

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NAME OF DRUG

PrAPO-PROPRANOLOL


(10, 20, 40, 80 and 120 mg Tablets)

USP

PHARMACOLOGIC CLASSIFICATION

Beta-adrenergic receptor blocking agent

ACTIONS

APO-PROPRANOLOL (propranolol hydrochloride) is a beta-adrenergic receptor blocking

agent. It has no other autonomic nervous system activity. Propranolol hydrochloride is a

competitive antagonist which specifically competes with beta-adrenergic receptor stimulating

agents for available beta receptor sites.

When access to beta-adrenergic receptor sites is blocked by propranolol hydrochloride, the

chronotropic, inotropic, and vasodilator responses to beta-adrenergic stimulation are

decreased proportionately.

Beta-adrenergic blockade is useful in some clinical conditions in which sympathetic activity

is excessive or inappropriate, and therefore detrimental to the patient. Sympathetic

stimulation is however, vital in some situations, (e.g. in patients with A-V block or with a

severely damaged: heart) and should, be preserved. The basic objective of beta-adrenergic

blockade is to decrease adverse sympathetic stimulation but not to the degree that impairs

necessary sympathetic support. Beta-blockade results in bronchial constriction by interfering

with endogenously or exogenously induced bronchodilation. (See CONTRAINDICATIONS

and WARNINGS).

The mechanism of the antihypertensive effects of propranolol hydrochloride has not been

established. Among the factors that may be involved are (1) decreased cardiac output, (2)

inhibition of renin release by the kidneys, and (3) diminution of tonic sympathetic nerve

outflow from vasomotor centers in the brain. It has been suggested, but not established, that

propranolol hydrochloride may achieve a better antihypertensive effect in patients with

normal or elevated plasma renin activity than those with low PRA.

Propranolol hydrochloride may reduce the oxygen requirement of the heart at any level of

effort by blocking catecholamine-induced increases in the heart rate, systolic blood pressure,

and the velocity and extent of myocardial contraction. On the other hand, propranolol

hydrochloride may increase oxygen requirements by increasing left ventricular fiber length,

and diastolic pressure, and systolic ejection period. When the net effect is beneficial in

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anginal patients, it manifests itself during exercise or stress by delaying the onset of pain and

reducing the incidence and severity of anginal attacks.

Propranolol hydrochloride exerts antiarrhythmic effects in concentrations producing beta-

adrenergic blockade, which appears to be its principal antiarrhythmic mechanism of action.

Beta-adrenergic blockade is of importance in the management of arrhythmias caused by

increased levels of circulating catecholamines or enhanced sensitivity of the heart to

catecholamines (arrhythmias associated with pheochromocytoma, thyrotoxicosis, and

exercise).

Propranolol hydrochloride is almost completely absorbed from the gastrointestinal tract and

undergoes extensive presystemic (or 'first pass') elimination due to its high hepatic clearance.

Interindividual variations in circulating drug concentrations due to this "first pass effect"

have been documented and differ according to a number of factors including genetic make-

up.

Peak plasma concentrations of propranolol hydrochloride are attained in 60-90 minutes. The

plasma half-life is approximately 3 hours whereas the duration of pharmacological effect is

longer.

INDICATIONS

APO-PROPRANOLOL is indicated in the treatment of mild to moderate hypertension and

for the prophylaxis of angina pectoris

APO-PROPRANOLOL is compatible with thiazide-like diuretics and/or peripheral

vasodilators. Combinations of APO-PROPRANOLOL with thiazide-like diuretics and/or

peripheral vasodilators have been shown to be generally more effective than propranolol

alone.

APO-PROPRANOLOL is not recommended for the emergency treatment of hypertensive

crises.

Geriatrics: There is no information available for elderly patients.

Pediatrics: APO-PROPRANOLOL is not recommended for use in children (see

WARNINGS AND PRECAUTIONS, Special Populations).

A. CARDIAC ARRHYTHMIAS

1. Supraventricular arrhythmias

a) Paroxysmal atrial tachycardias, particularly those arrhythmias

induced by catecholamines or digitalis or associated with Wolff-

Parkinson-White syndrome (see W-P-W under WARNINGS) .

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b) Persistent sinus tachycardia which is non-compensatory and impairs the

well-being of the patient.

c) Tachycardias and arrhythmias due to thyrotoxicosis when causing

distress or increased hazard and when immediate effect is necessary as

adjunctive, short-term therapy (e.g. 2 to4 weeks) . May be used with,

but not in place of, specific therapy (see Thyrotoxicosis under

WARNINGS) .

d) Persistent atrial extrasystoles which impair the well-being of the patient

and do not respond to conventional measures.

e) Atrial flutter and fibrillation when ventricular rate cannot be controlled

by digitalis alone, or when digitalis is contraindicated.

2. Tachyarrhythmias of digitalis intoxication.

If digitalis-induced tachyarrhythmias persist following discontinuance of

digitalis and correction of electrolyte abnormalities, they may be

reversible with APO-PROPRANOLOL. Severe bradycardia may occur,

(See SYMPTOMS AND TREATMENT OF OVERDOSAGE) .

B. MIGRAINE

APO-PROPRANOLOL is indicated for the prophylaxis of migraine headache. It

is not indicated for the treatment of acute migraine attacks.

C. HYPERTROPHIC SUBAORTIC STENOSIS

APO-PROPRANOLOL is useful in the management of hypertrophic subaortic

stenosis, especially for the treatment of exertional or other stress-induced angina,

palpitations, and syncope. APO-PROPRANOLOL may also improve exercise

performance. The effectiveness of propranolol hydrochloride in this disease appears

to be due to a reduction of the elevated outflow pressure gradient which is

exacerbated by beta-adrenergic receptor stimulation. Clinical improvement may be

temporary.

D. PHEOCHROMOCYTOMA

After primary treatment with an alpha-adrenergic blocking agent has been instituted,

APO-PROPRANOLOL may be useful as adjunctive therapy if the control of

tachycardia becomes necessary before or during surgery.

It is hazardous to use APO-PROPRANOLOL unless alphaadrenergic blocking

drugs are already in use, since this would predispose to serious blood pressure

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rise. Blocking only the peripheral dilator (beta) action of epinephrine leaves its

constrictor (alpha) action unopposed. In the event of hemorrhage or shock,

producing both beta- and alpha-blockade is contraindicated since the

combination prevents the increase in heart rate and peripheral vasoconstriction

needed to maintain blood pressure.

In inoperable or metastatic pheochromocytoma, APOPROPRANOLOL may

be useful as an adjunct to the management of symptoms due to excessive beta-

adrenergic receptor stimulation.

CONTRAINDICATIONS

APO-PROPRANOLOL (propranolol hydrochloride) is contraindicated in:

bronchospasm including bronchial asthma;

allergic rhinitis during the pollen season;

sinus bradycardia and greater than first degree block;

cardiogenic shock;

right ventricular failure secondary to pulmonary hypertension;

congestive heart failure (See WARNINGS) unless the failure is secondary to a

tachyarrhythmia treatable with APO-PROPRANOLOL.

patients prone to hypoglycaemia, i.e. after prolonged fasting or patients with impaired

capacity to counter-regulate a possible hypoglycaemic event.

As with other beta-blockers, APO-PROPRANOLOL must not be used in patients with

any of the following:

in patients with bradycardia;

hypotension;

metabolic acidosis;

severe peripheral arterial circulatory disturbance;

sick sinus syndrome;

untreated pheochromocytoma;

uncontrolled heart failure;

Prinzmetal’s angina.

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Due to the presence of lactose in the 20 and 120 mg APO-PROPRANOLOL tablets,

use in patients with hereditary problems of galactose intolerance, glucose-galactose

malabsorption or the Lapp lactase deficiency is also contraindicated (see WARNINGS

AND PRECAUTIONS, Sensitivity/Resistance).

WARNINGS AND PRECAUTIONS

CARDIAC FAILURE

Sympathetic stimulation is a vital component supporting circulatory function in congestive

heart failure; therefore, inhibition by means of beta-adrenergic blockade is a potential hazard

as it may further depress myocardial contractility and precipitate cardiac failure.

APO-PROPRANOLOL (propranolol hydrochloride) acts selectively without abolishing the

inotropic action of digitalis on the heart muscle (i.e., that of supporting the strength of

myocardial contractions). In patients already receiving digitalis, the positive inotropic action

of digitalis may be reduced by propranolol hydrochloride's negative inotropic effect. The

effects of propranolol hydrochloride and digitalis are additive in depressing A-V conduction.

IN PATIENTS WITHOUT A HISTORY OF CARDIAC FAILURE

Continued depression of the myocardium over a period of time can in some patients, lead to

cardiac failure. In rare instances, this has been observed during propranolol hydrochloride

therapy. Therefore, at the first sign of symptoms of impending cardiac failure, patients should

be fully digitalized and/or given a diuretic, and the response observed closely:

If cardiac failure continues, despite adequate digitalization and diuretic therapy,

APO-PROPRANOLOL should be withdrawn immediately.

If tachyarrhythmia is being controlled, patients should be maintained on

combined therapy and closely followed until threat of cardiac failure is over.

ABRUPT CESSATION OF THERAPY IN ANGINA PECTORIS

Severe exacerbation of angina and the occurrence of myocardial infarction have been reported

in some patients with angina pectoris following abrupt discontinuation of propranolol

hydrochloride therapy. Therefore, when discontinuation of APO-PROPRANOLOL is

planned in patients with angina pectoris, the dosage should be gradually reduced over a

period of about two weeks and the patient should be carefully observed. The same

frequency of administration should be maintained. In situations of greater urgency, APO-

PROPRANOLOL dosage should be reduced stepwise, in four days under close

observation. If angina markedly worsens, or acute coronary insufficiency develops, it is

recommended that treatment with APO-PROPRANOLOL be reinstituted promptly, at

least temporarily. In addition, patients with angina pectoris should be warned against

abrupt discontinuation of APO-PROPRANOLOL.

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OCULOMUCOCUTANEOUS SYNDROME

Various skin rashes and conjunctival xerosis have been reported in patients treated with

beta-blockers including APO-PROPRANOLOL. A severe oculomucocutaneous syndrome,

whose signs include conjunctivitis sicca and psoriasiform rashes, otitis, and sclerosing

serositis has occurred with the long-term use of one beta-adrenergic blocking agent. This

syndrome has not been observed with propranolol hydrochloride, however, physicians

should be alert to the possibility of such reactions and discontinue treatment if they occur.

IN PATIENTS WITH THYROTOXICOSIS

Possible deleterious effects from long-term use of propranolol hydrochloride have not yet

been adequately appraised. Special consideration should be given to propranolol

hydrochloride's potential for aggravating congestive heart failure. Propranolol hydrochloride

may mask the clinical signs of developing or continuing hyperthyroidism or its

complications, and may give a false impression of improvement. Therefore, abrupt

withdrawal of APO-PROPRA.NOLOL may be followed by an exacerbation of symptoms of

hyperthyroidism, including thyroid storm. This may be another instance where APO-

PROPRANOLOL should be withdrawn slowly by reducing dosage. Propranolol

hydrochloride does not distort thyroid function tests.

IN PATIENTS WITH WOLFF-PARKINSON-WHITE SYNDROME

APO-PROPRANOLOL should be used with caution since several cases have been

reported in which, after propranolol hydrochloride treatment, the tachycardia was

replaced by a severe bradycardia requiring a demand pacemaker. In one patient, this

occurred after an initial dose of 5 mg of propranolol hydrochloride.

IN PATIENTS UNDERGOING ELECTIVE OR EMERGENCY SURGERY

The management of patients with angina, being treated with beta-blockers and undergoing

elective or emergency surgery, is controversial because beta-adrenergic receptor blockade

impairs the ability of the heart to respond to beta-adrenergically mediated reflex stimuli, but

abrupt discontinuation of therapy with APO-PROPRANOLOL may be followed by severe

complications. (See WARNINGS). Some patients receiving beta-adrenergic blocking agents

have been subject to protracted severe hypotension during anesthesia. Difficulty in restarting

and maintaining the heartbeat has also been reported.

For these reasons, in patients with angina undergoing elective surgery, APO-

PROPRANOLOL should be withdrawn gradually following the recommendation given under

Abrupt Cessation of Therapy. (See WARNINGS). According to available evidence, all

clinical and physiologic effects of beta-blockade are no longer present 48 hours after cessation

of medication.

In emergency surgery, since APO-PROPRANOLOL is a competitive inhibitor of beta-

adrenergic receptor agonists, its effects may be reversed, if necessary, by sufficient doses of

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such agonists as isoproterenol or levarterenol.

Anesthesia with agents which maintain cardiac contractility by virtue of their effect on

catecholamine release (e.g. ether) should be avoided in patients on APO-PROPRANOLOL

therapy.

IN PATIENTS PRONE TO NON-ALLERGIC BRONCHOSPASM

(e.g. Chronic Bronchitis, Emphysema, Bronchiectasis),

APO-PROPRANOLOL, should be administered with caution since it may block

bronchodilation produced by endogenous and exogenous catecholamine stimulation of beta-

adrenergic receptors.

IN PATIENTS WITH DIABETES AND IN THOSE SUBJECT TO HYPOGLYCEMIA

APO-PROPRANOLOL, because of its beta-adrenergic blocking activity, may block

premonitory signs and symptoms (pulse rate and pressure changes) of acute hypoglycemia.

This is especially important to keep in mind in patients with labile diabetes. Hypoglycemic

attacks may be accompanied by a precipitous elevation of blood pressure.

USE IN PREGNANCY

The safe use of propranolol hydrochloride in pregnancy has not been established. Use of any

drug in pregnancy or in women of child-bearing potential requires that the possible risk to

mother and/or fetus be weighed against the expected therapeutic benefit. Perinatal

complications, such as small placenta and intra-uterine growth retardation, have been reported

in a few cases where the mother took propranolol hydrochloride during pregnancy. Some

infants born to mothers treated with propranolol hydrochloride were reported to have

hypoglycemia and/or bradycardia.

USE IN CHILDREN

While experience with propranolol hydrochloride in children under 12 is limited, the

indications for which APO-PROPRANOLOL is recommended occur infrequently in

childhood. Although reports fail to indicate that children respond in a manner different from

the adult, physicians are advised to undertake treatment with caution.

Hypersensitivity, Allergic Reactions

Anaphylactic/anaphylactoid reactions have been associated with the administration of

propranolol hydrochloride (see ADVERSE REACTIONS). There may be increased difficulty

in treating an allergic type reaction in patients on beta-blockers. In these patients, the reaction

may be more severe due to pharmacological effects of beta-blockers and problems with fluid

changes. Epinephrine should be administered with caution since it may not have its usual

effects in the treatment of anaphylaxis. On the one hand, larger doses of epinephrine may be

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needed to overcome the bronchospasm, while on the other, these doses can be associated with

excessive alpha adrenergic stimulation with consequent hypertension, reflux bradycardia and

heart-block and possible potentiation of bronchospasm. Alternatives to the use of large doses

of epinephrine include vigorous supportive care such as fluids and the use of beta agonists

including parenteral salbutamol or isoproterenol to overcome bronchospasm, and

norepinephrine to overcome hypotension.

Sensitivity/Resistance Due to the presence of lactose in the 20 and 120 mg APO-PROPRANOLOL tablets, patients

with hereditary problems of galactose intolerance, glucose-galactose malabsorption or the

Lapp lactase deficiency should not take the 20 or 120 mg tablets of APO-PROPRANOLOL.

Some slowing of heart due to unopposed vagal activity is usual in patients receiving APO-

PROPRANOLOL (propranolol hydrochloride), however, occasionally severe bradycardia

occurs and may lead to vertigo, syncopal attacks or orthostatic hypotension. Patients,

especially those with limited cardiac reserve should be monitored for signs of excessive

bradycardia. Should the patient become symptomatic the dose of APO-PROPRANOLOL

should be decreased or, if necessary, the drug should be discontinued. If it is essential to

correct the bradycardia intravenous atropine or isoproterenol should be considered.

It has been reported that administration of propranolol hydrochloride to control cardiac

arrhythmias in acute myocardial infarction has caused marked reduction in cardiac output.

Therefore, the doses of APO-PROPRANOLOL should be kept to the minimum in patients

with severe myocardial infarction. Prior administration of other antiarrhythmic cardiac

depressant drugs, such as procainamide or quinidine may potentiate the cardiac-depressant

activities of APO-PROPRANOLOL. Prior digitalization may be indicated and atropine should

be at hand to control bradycardia.

The combination of propranolol hydrochloride with a thiazide-like diuretic and/or peripheral

vasodilator produces a greater fall in blood pressure than either drug alone. This occurs

regardless of which drug is administered first. The same degree of blood pressure control can

be achieved by lower than usual dosages of each drug. Therefore, when using such combined

therapy, careful monitoring of the dosages is required until the patient is stabilized.

Patients receiving catecholamine depletion drugs such as reserpine or guanethidine should be

closely observed if APO-PROPRANOLOL is administered concomitantly. The added

catecholamine blocking action of this drug may produce an excessive reduction of the resting

sympathetic nervous activity.

In patients on long-term treatment with APO-PROPRANOLOL, laboratory determinations

should be made at regular intervals. The drug should be used with caution in patients with

impaired renal and hepatic functions.

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ADVERSE REACTIONS

The most serious adverse effects that may be encountered with APO-PROPRANOLOL

(propranolol hydrochloride) are congestive heart failure and bronchospasm (See

CONTRAINDICATIONS, WARNINGS and PRECAUTIONS).

Gastrointestinal disturbances (anorexia, nausea, vomiting, diarrhea, abdominal pain) are the

most common adverse effects reported. Other less frequently reported adverse effects are: (in

descending order) cold extremities and exacerbation of Raynaud's phenomenon; congestive

heart failure; sleep disturbances including vivid dreams; dizziness, fatigue and bronchospasm.

Reported adverse effects, according to organ systems are recorded below:

CARDIOVASCULAR

Congestive heart failure (see WARNINGS); heart failure deterioration; precipitation of heart

block; secondary effects of decreased cardiac output (which could include: syncope, vertigo,

lightheadedness, decreased renal perfusion and rarely, postural hypotension); intensification

of AV block and hypotension; severe bradycardia; claudication and cold extremities,

Raynaud’s phenomenon; dyspnoea; palpitations; precordial pain.

CENTRAL NERVOUS SYSTEM

Dizziness, lethargy, weakness, drowsiness, headache, insomnia, fatigue, anorexia, anxiety,

mental depression, poor concentration, reversible amnesia and catatonia, vivid dreams with or

without insomnia, nightmares, psychoses, mood changes, confusion, hallucinations,

paresthesia, incoordination.

GASTROINTESTINAL

Nausea, vomiting, epigastric distress, anorexia, bloating, mild diarrhea, constipation.

RESPIRATORY

Bronchospasm (may occur in patients with bronchial asthma or a history of asthmatic

complaints, sometimes with fatal outcome); laryngospasm and respiratory distress (see

CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS).

Blood

Thrombocytopenia

DERMATOLOGIC

A few cases of erythematous rashes and increase of facial acneiform lesions have been

reported; urticaria; exfoliative psoriasiform eruption; Stevens-Johnson Syndrome; toxic

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epidermal necrolysis, exfoliative dermatitis and erythema multiforme.

Endocrine

Hypoglycaemia in elderly patients, patients on haemodialysis, patients on concomitant

antidiabetic therapy, patients with prolonged fasting and patients with chronic liver disease

(see CONTRAINDICTIONS and WARNINGS AND PRECAUTIONS).

Allergic

Hypersensitivity reactions, including anaphylactic/anaphylactoid reactions. A few cases of

erythematous rashes and increase of facial acneiform lesions have been reported; urticaria;

exfoliative psoriasiform eruption.

OTHERS

Reduction or loss of libido; reversible alopecia and rarely: diminution and loss of hearing;

tinnitus, visual disturbances; diminished vision; conjunctivitis; thrombocytopenic purpura;

pharyngitis and agranulocytosis, fever combined with aching and sore throat; urinary retention

associated with repeated bouts of paroxysmal tachycardia; flushing of the face.

CLINICAL LABORATORY TESTING FINDINGS

Elevated blood urea levels in patients with severe heart disease, elevated serum transaminase,

alkaline phosphatase, and lactate dehydrogenase have been reported. An increase in ANA

(antinuclear antibodies) has been observed, however the clinical relevance of this is not clear.

SYMPTOMS AND TREATMENT OF OVERDOSAGE

Several reports in the published literature describe cases in which propranolol hydrochloride

was used as a suicide agent. In most cases, other agents, e.g. alcohol, have also been involved.

One patient who was thought to have ingested 3,600 mg of propranolol hydrochloride died.

Survival of patients taking higher single doses has, however, also been reported.

The common signs to be expected in overdosage are bradycardia, hypotension,

bronchospasm, or acute cardiac failure. If overdosage occurs, in all cases therapy with APO-

PROPRANOLOL should be discontinued and the patient observed closely. In addition the

following therapeutic measures are suggested:

BRADYCARDIA

Administer atropine incrementally in 0.6 mg doses. If there is no response to vagal blockade,

administer isoproterenol cautiously.

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CARDIAC FAILURE

Digitalization and Diuretics

HYPOTENSION

Vasopressors, e.g. levarterenol or epinephrine. (See Precaution concerning the use of

epinephrine in beta-blocked patients).

BRONCHOSPASM

Administer isoproterenol and aminophylline.

DRUG INTERACTIONS

Drug-Drug Interactions

The drug interactions discussed in this section are based on either drug interactions case

reports or studies, or potential interaction due to expected magnitude and seriousness of the

interaction.

Anti-arrhythmic drugs

- Class I anti-arrhythmic drugs (e.g. disopyramide) and amiodarone may have a

potentiating effect on atrial-conduction time and induce negative inotropic effects.

- Other cardiac-depressant anti-arrhythmic drugs: prior administration of other

antiarrhythmic drugs, such as procainamide and quinidine may potentiate the cardiac-

depressant activity of propranolol hydrochloride. Prior digitalization may be indicated

and atropine should be at hand to control bradycardia.

Thiazide-like diuretics and peripheral vasodilators: The combination of propranolol

hydrochloride with a thiazide-like diuretic and/or a peripheral vasodilator produces a greater

fall in blood pressure than either drug alone. This occurs regardless of which drug is

administered first (see WARNINGS AND PRECAUTIONS, General).

Reserpine or guanethidine: Patients receiving catecholamine depleting drugs should be closely

observed if administered concomitantly with APO-PROPRANOLOL. The added

catecholamine blocking action of these drugs may produce an excessive reduction in the

resting sympathetic nervous activity.

Rizatriptan: The simultaneous administration of rizatriptan and propranolol can increase the

rizatriptan AUC and Cmax by approximately 70-80%. The increased rizatriptan exposure is

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presumed to be caused by inhibition of first-pass metabolism of rizatriptan through inhibition

of monoamine oxidase-A. If both drugs are to be used, a rizatriptan dose of 5 mg has been

recommended.

Digitalis glycosides: In association with beta-blockers, digitalis glycosides may increase

atrioventricular conduction time.

Verapamil, Diltiazem: Beta-blockers combined with calcium channel blockers with negative

inotropic effects (such as verapamil and diltiazem) can lead to an exaggeration of these

effects, particularly in patients with impaired ventricular function and/or SA or AV

conduction abnormalities. This may result in severe hypotension, bradycardia and cardiac

failure. Neither the beta-blocker nor the calcium channel blocker should be administered

within 48 hours of discontinuing the other.

Nifedipine: concomitant therapy with dihydropyridine calcium channel blockers (such as

nifedipine) may increase the risk of hypotension and cardiac failure may occur in patients

with latent cardiac insufficiency.

Fingolimod: Concomitant use of fingolimod with beta blockers may potentiate bradycardic

effects and is not recommended. Where such coadministration is considered necessary,

appropriate monitoring at treatment initiation, i.e. at least overnight monitoring, is

recommended.

Epinephrine: Concomitant use of sympathomimetic agents, such as epinephrine, may

counteract the effects of beta-blockers. Caution must be exercised when administering

epinephrine parenterally to patients taking beta-blockers as, in rare cases, vasoconstriction,

hypertension and bradycardia may result.

Lidocaine: administration of propranolol hydrochloride during an infusion of lidocaine may

increase the plasma concentration of lidocaine by approximately 30%. Patients already

receiving propranolol hydrochloride tend to have higher lidocaine levels than controls. The

combination should be avoided.

Cimetidine: Concomitant use of cimetidine will increase plasma levels of propranolol.

Alcohol: Concomitant use of alcohol may increase the plasma levels of propranolol.

Clonidine: Beta-blockers may exacerbate the rebound hypertension which can follow the

withdrawal of clonidine. If clonidine is co-administered with a beta-blocker, the beta-blocker

should be withdrawn several days before stopping clonidine administration. If replacing

clonidine with beta-blocker therapy, the introduction of the beta-blocker should be delayed for

several days after clonidine has been discontinued.

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Ergotamine, Dihydroergotamine (and related compounds); Caution must be exercised if

ergotamine, dihydroergotamine or related compounds are given in combination with

propranolol hydrochloride, since vasospastic reactions have been reported in a few patients.

Ibuprofen, Indomethacin: Concomitant use of prostaglandin synthetase inhibiting drugs (e.g.

ibuprofen and indomethacin) may decrease the hypotensive effects of propranolol

hydrochloride.

Chlorpromazine: The concomitant use of propranolol hydrochloride and chlorpromazine may

result in an increase in plasma levels of both drugs. This may lead to an enhanced

antipsychotic effect of chlorpromazine and an increased antihypertensive effect of APO-

PROPRANOLOL.

Anaesthetic agents: Use of beta-blockers with anaesthetic agents may result in attenuation of

the reflex tachycardia and increase the risk of hypotension. Anaesthetic agents causing

myocardial depression should be avoided and caution should be exercised when using any

anaesthetic agents with APO-PROPRANOLOL. If anaesthesia is required, the anaesthetist

should be informed that the patient has been taking APO-PROPRANOLOL and the choice of

anaesthetic should be one with as little negative inotropic activity as possible.

Other medications: Pharmacokinetic studies have shown that several drugs may interact with

propranolol due to effects on enzyme systems in the liver, which metabolizes propranolol and

the following agents: quinidine, propafenone, rifampicin, theophylline, warfarin, thioridazine

and dihydropyridine calcium channel blockers, such as nifedipine, nisoldipine, nicardipine,

isradipine, and lacidipine. Owing to the fact that blood concentrations of either agent may be

affected, dosage adjustments may be needed according to clinical judgement. (See also the

section above on Nifedipine).

Drug-Food Interactions

Interactions with food have not been established.

Drug-Herb Interactions

Interactions with herbal products have not been established.

Drug-Laboratory Interactions

Propranolol hydrochloride does not interfere with thyroid function tests.

Interactions with other laboratory tests have not been established.

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DOSAGE AND ADMINISTRATION

HYPERTENSION

Therapeutic, response to a given dosage varies between patients, therefore, dosage must be

individually titrated and should be carefully monitored. In the treatment of hypertension APO-

PROPRANOLOL (propranolol hydrochloride) may be started by administering the drug in

two equal daily doses of 40 mg. This may be increased, if necessary, in one week, to 80 mg

twice daily, before breakfast and at bedtime. If necessary, the drug may be increased to 160

mg twice daily. For most patients the dosage is within the range of 160 to 320 mg daily. A

small number of patients may respond to 80 mg daily. Experience to date suggests that in

some resistant patients increasing the dosage above 320 mg/day may have an additional

effect. Doses above 320 mg/day should be given on a t.i.d. or q.i.d. regimen.

The time course of full blood pressure response is variable. The anti-hypertensive effect will

usually occur within 3 to 7 days after reaching the effective dose. The maximum decrease in

blood pressure may occur 2 to 4 weeks after initiation of treatment.

ANGINA PECTORIS

Dosage must be individualized. Starting with 10 to 20 mg three or four times daily, before

meals and at bedtime, dosage should be gradually increased at 3 to 7 day intervals until

optimum response is obtained. Although individual patients may respond at any dosage level,

the average optimum dosage appears to be 160 mg/day. Occasionally, in resistant patients,

dosage as high as 320 to 400 mg/day have been administered with beneficial results. If

treatment is to be discontinued, reduce dosage gradually over a period of about two weeks

(See WARNINGS).

ARRHYTHMIAS

10 to 30 mg three or four times daily, before meals and at bedtime.

MIGRAINE

Dosage must be individualized. The initial dose is 40 mg twice daily. The dose may then be

gradually increased until optimum migraine prophylaxis is achieved. The usual effective dose

range is 80 to 160 mg/day.

HYPERTROPHIC SUBAORTIC STENOSIS

20 to 40 mg three or four times daily, before meals and at bedtime.

PHEOCHROMOCYTOMA

Pre-operatively - 60 mg daily, in divided doses, for three days before surgery, concomitantly

with an alphareceptor blocking agent.

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Malignant cases - 30 mg daily, in divided doses.

STORAGE AND STABILITY

Store at room temperature (15oC to 30oC).

Keep out of the reach and sight of children.

AVAILABILITY

APO-PROPRANOLOL is available in the following dosage forms:

Tablets 10 mg: Orange, round, biconvex tablet. Scored & engraved APO over 10 on

one side, other side plain. Bottles of 100 and 1000 tablets.

Tablets 20 mg: Blue, hexagonal, biconvex tablet. Scored & engraved APO over 20 on


Tablets 40 mg: Green, round, biconvex tablet. Scored & engraved APO over 40 on one

side, other side plain. Bottles of 100 and 1000 tablets.

Tablets 80 mg: Yellow, round, biconvex tablet. Scored & engraved APO over 80 on


Tablets 120 mg: Reddish-pink, round, biconvex tablet. Scored & engraved APO over

120 on one side, other side plain. Bottles of 100 and 1000 tablets.

COMPOSITION

APO-PROPRANOLOL (propranolol hydrochloride) tablets contain the following non-

medicinal ingredients (in alphabetical order): Brilliant Blue Lake (20 mg, 40 mg), Ferric

Oxide (120 mg), Lactose (20 mg and 120 mg), Indigotine Lake (20 mg), magnesium

stearate, microcrystalline cellulose and starch (10 mg, 40 mg and 80 mg), Sunset Yellow

Lake (10 mg) and Tartrazine Lake (40 mg, 80 mg).

of 26

PHARMACEUTICAL INFORMATION

Drug Substance

Proper name: Propranolol Hydrochloride

Chemical Name: (±) 1-(isopropylamino)-3-(1-naphthyloxy)-2-propanol

hydrochloride

Molecular formula: C16H22ClNO2

Molecular weight: 295.81 g/mol

Structural formula:

Physicochemical properties: Propranolol hydrochloride is a stable, colorless,

crystalline solid with a melting point of 163-164°C. It is

readily soluble in water and ethanol and insoluble in

nonpolar solvents.

PHARMACOKINETICS

Propranolol hydrochloride is rapidly and almost completely absorbed from the

gastrointestinal tract. A large part of the absorbed drug is lost to the systemic circulation due

to the first pass metabolism in the liver. After repeated administration, the first pass removal

process becomes saturated and, at steady state, the plasma concentration is proportional to

the dose, although there is some variation between patients as to the blood levels achieved at

a given dose. In addition, correlation of plasma level to therapeutic effect varies considerably

with propranolol hydrochloride as with some other beta-blockers. This lack of correlation is

most marked in the treatment of angina and hypertension.

of 26

The circulating drug is more than 90% bound to serum proteins. Propranolol hydrochloride is

rapidly and extensively metabolized and excreted by the kidney. Over 20 metabolites have

been identified. One of these, the 4-hydroxy metabolite, found only after oral administration,

has beta-adrenergic blocking properties. The biological half-life of APO-PROPRANOLOL

(i.e. the serum concentration of the unchanged drug) is about four hours. The duration of

pharmacologic effect is longer.

PHARMACOLOGY

Propranolol hydrochloride is a competitive antagonist of endogenous and exogenous

sympathomimetic amines at the beta-adrenergic receptors (Beta1 and Beta2). Chemically it is

a racemic mixture of equal amounts of levo and dextro isomers. The levo isomer is

responsible for most of the beta-receptor blocking activity.

CARDIOVASCULAR EFFECTS

Intravenous administration of propranolol to cats and dogs produced a fall in heart rate by

blocking endogenous sympathetic activity to the heart. In anesthetized dogs, propranolol

produced dose-related decrease in heart rate, cardiac contractile force, and small depressions

in blood pressure, and cardiac output. These effects have also been demonstrated in man. A

reduction in oxygen consumption and increased right atrial pressure were observed in human

myocardium.

Human and animal studies with propranolol have demonstrated competitive and reversible

blockade of the increased heart rate and increased force of contraction produced by

isoproterenol, adrenaline, noradrenaline and stellate ganglion stimulation. Propranolol

reduced the pressor response of noradrenaline, potentiated that of adrenaline, but did not

effect the response of phenylephrine.

Epstein and associates studied 16 human subjects under conditions of maximal and

submaximal exercise. Propranolol 0.15 mg/kg intravenously, was sufficient to reduce by

tenfold the sensitivity of heart rate to isoproterenol.

Blockade of beta-adrenergic receptors in the peripheral vasculature has little if any effect on

circulation or blood pressure. Administered intra-arterially, propranolol causes a brief

vasodilation unrelated to beta-adrenergic receptor blockade.

Amounts of propranolol which completely abolished the increase in heart rate produced by

stimulation of the right stellate ganglion in anesthetized cats did not affect the bradycardia

produced by vagal stimulation.

Propranolol causes no observable response when it interacts with beta-receptors in the

absence of a primary agonist such as epinephrine or isoprenaline indicating a lack of intrinsic

sympathomimetic activity.

of 26

Lucchesi et al demonstrated in dogs that propranolol was effective in reversing or preventing

several types of experimentally-induced cardiac arrhythmias.

In animal experiments, at concentrations much higher than those necessary for complete beta-

adrenergic blockade, propranolol exerts a local anesthetic effect. This has also been termed a

"membrane stabilizing" or "quinidine-like" effect. This property of propranolol has been

demonstrated in vitro with human myocardium only at a minimum concentration of 10 mg/L

which is about 100 times greater than that required for inhibition of exercise tachycardia or

suppression of ectopic beats. This is, therefore, not thought to be an important property of

propranolol in the doses used in clinical practice and there are no in vivo methods for

demonstrating this effect in man.

Plasma renin activity is inhibited by propranolol.

RESPIRATORY EFFECTS

Propranolol increases airway resistance by inhibiting the sympathetic innervation of the

bronchi. This effect is small in most normal individuals where it can only be demonstrated by

measuring forced expiry volume (FEV 1). In asthmatics and patients with other

bronchospastic diseases however, this effect is marked and potentially dangerous.

Injection of propranolol reduced FEV1 with dyspnoea, cough and dizziness in two of eleven

patients with chronic obstructive lung disease. When given the drug orally (40 mg q.i.d.) five

of these eleven patients reported dyspnoea. Propranolol has been reported to potentiate

bronchospasm induced by histamine, acetylcholine, methylcholine or allergen and this

potentiation is greater in asthmatics than in non-asthmatic subjects.

Central Nervous System Effects

Propranolol hydrochloride readily crosses the blood/brain barrier. In some animal

experiments, it has been shown to display central muscle relaxant, sedative and anticonvulsant

properties. To date, none of these effects can be directly attributed to blockade of beta-

adrenergic receptors in the central nervous system. One publication, suggests that

propranolol's CNS activity may be attributable to a glycol metabolite.

Metabolic Activity

Propranolol hydrochloride may produce hypoglycemia but this effect appears to be rare and

its mechanism is not clear. Propranolol also impairs the sympathetically mediated rebound

response to hypoglycemic symptoms (see WARNINGS).

Propranolol hydrochloride inhibits the rise in plasma free fatty acids induced by

sympathomimetic amines. It also inhibits the lipolytic action of catecholamines in isolated

adipose tissues of several animal species.

of 26

TOXICOLOGY

Acute Oral Toxicity (LD50)

Mice: 620 mg./kg.

Rats: 638 mg. /kg.

Chronic Toxicity

It has been reported that a toxicity study of 18 months duration was conducted in four groups

of rats (one control and three experimental) each consisting of 25 males and 25 females. All

animals received medication by tube directly into the stomach for the first six months and

thereafter received the drug in the diet.

A number of animals who received the highest dose (150 mg/kg) developed bronchospasm

soon after receiving the drug. A variety of pathologic lesions were observed in both the

control and experimental groups. Dilatation of both ventricles was noted in a number of high-

dose experimental rats that died spontaneously during the early part of the experiment.

Spontaneous myocarditis consisting of minor lymphocytic infiltration was observed in both

groups. Testicular atrophy and reduction or absence of corpora lutea was seen in both

the control and experimental groups.

It has been reported that a one-year toxicity test was carried out in 32 dogs in both sexes,

divided into four groups (control and propranolol 60, 20 and 5 mg/kg). A patchy edema and a

slight increase in the size of the lymphoid follicles of the mucosa in the fundus of the stomach

were seen and were attributed to mild irritation caused by prolonged dosing with high doses

of propranolol.

It has been reported that the carcinogenic potential of propranolol hydrochloride was

investigated in mice and rats by chronic administration of the compound in the diet for 78

weeks at varying concentrations to provide dosage levels of 10, 50 and 150 mg/kg/day.

Control groups of mice and rats were fed the same diet without compound. After 78 weeks of

administration, the mice were kept alive for an additional two months and the rats for six

months withdrawal period. At the termination of the experiment, gross and microscopic

pathologic investigations revealed that in mice the incidence of benign and malignant

neoplasms was similar in control and all treated groups. Thus, no compound-related,

tumorigenic effect was observed at any dose level. Similarly, no tumorigenic effect was found

in the rat. The tumor incidence was lower in female rats treated with 150 mg/kg/day

propranolol than in any of the other groups. This was attributed to the markedly decreased

body weight gains in this group.

It has been reported that to determine the effects of propranolol hydrochloride in rats on

fertility, pregnancy, the developing fetus, and newborns up to the time of weaning, various

dose levels of the drug were administered either by gastric intubation or in the feed. The drug

was also fed to rabbits in their diet. In some studies in rats a non-dose related increase in

of 26

resorption sites and neonatal deaths were observed. No teratogenic effects were noted in either

species. Furthermore, the compound had no adverse effect on fertility, pregnancy, parturition,

or lactation.

of 26

REFERENCES

1. Black, J.W., Duncan, W.A.M. and Shanks, R.G.: Comparison of Some Properties of

Pronethalol and Propranolol. Br. J. Pharmacol. & Chemother. 25:577, 1965.

2. Epstein, S.E., Robinson, B.F., Kahler, R.C. and Braunwald, E.: Effects of

Betaadrenergic Blockade on the Cardiac Response to Maximal and Submaximal

Exercise in Man. J. Clin. Invest. 44:1745, 1965.

3. Marshall, R.J., Barnes, W.E., Beane, J.E., Mallo, J.A, and Schwab, L.T.: Blockade

by Propranolol of the Hemodynamic and Metabolic Responses to Infused

Catecholamines. Abstr. Fed. Proc. 24:7l3 (Mar.-Apr.) Part I, 1965.

4. Troyer, W.G., Wallace, A.G., Lesage, M.A., Zotti, E.F. and Stead, E.A.:

Electrophysiologic Effects of Adrenergic Stimulation and Blockade. Abstr. Fed.

Proc. 24:713 (Mar.-Apr.) Part I, 1965.

5. Lucchesi, E.R., Whitsitt, L.S. and Brown N.L.: Propranolol in Experimentally

Induced Cardiac Arrhythmias. Can. J. Physiol. & Pharmacol. 44:543, 1966.

6. Shanks, R.G.: The Effect of Propranolol on the Cardiovascular Responses to

Isoprenaline, Adrenaline and Noradrenaline in the Anesthetized Dog. Br. J.

Pharmacol. & Chemother. 26:322, 1966.

7. Shanks, R.G.: The Peripheral Vascular Effects of Propranolol and Related

Compounds. Br. J. Pharmac. Chemother. 29:204, 1967.

8. Barrett, A.M. and Cullum, V.A.: The Biological Properties of the Optimal Isomers

of Propranolol and their Effects on Cardiac Arrhythmias. Br. J. Pharm. 34:43, 1968.

9. Dollery, C.T., Patterson, J.W. and Conolly, M.E.: Clinical Pharmacology of

Betareceptor-blocking Drugs. Clin. Pharm. Ther. 10:765, 1969.

10. Tivenius, L. and Nyberg, G.: Effect of Alprenolol and Propranolol on Ventilatory

Function. A Comparative Study in Patients with Chronic Obstructive Lung Disease.

Pharmacologic Clinica 2:51, 1969.

11. Gayrard, P., Orehek, J. and Charpin, J.: Le test au Propranolol: Nouveau Test de

Provaction de l'Asthme. Etude Comparative. Revue Tuberculose et de Pneumonogic.

35:5ll, 1971.

12. Greenblatt, D.J. and Shader, R.I.: On the Psychopharmacology of Beta-adrenergic

Blockade. Current Ther. Res. 14:6l5, 1972.

13. Saelens, D.A., Walle, T., Privitera, P.J. et al.: Central Nervous System Effects and

Metabolic Disposition of a Glycol Metabolite of Propranolol. J. Pharmacol. Exp.

188:86, 1974.

14. Meyler’s Side Effects of Drugs: Vol. 8, p. 443, Excerpta Medica, Amsterdam-

Oxford, American Elsevier Publishing Co. Inc. New York. 1975.

15. Nickerson. M. and Collier, B.: Propranolol and Related Drugs. The Pharmacological

Basis of Therapeutics eds. L.S. Goodman and A. Gilman. MacMillan Publishing Co.

Inc. N.Y. 5th Edition, 1975.

16. Nies, A.S. and Shand, D.G.: Clinical Pharmacology of Propranolol Circulation. 52:6,

1975.

17. Conolly, M.E., Kersting, F. and Dollery, C.T.: The Clinical Pharmacology of Beta-

Adrenoceptor-Blocking Drugs. Prog.Cardiovasc. Disease, Vol. XIX, No.3, 1976.

18. Johnsson, G. and Regardh, C.G.: Clinical Pharmacokinetics of β-adrenoreceptor

of 26

Blocking Drugs. Clin. Pharmacokinet. l:233, 1976.

19. Shand, D.G.: Pharmacokinetics of Propranolol: A Review Postgrad. Med. J. 52

(Suppl.4):22. 1976.

20. Beumer, H.M.: Adverse Effects of β-adrenoreceptor Blocking Drugs on Respiration.

Cardiovascular Drugs. ed. G.S. Avery, Vol. 2: β-adrenoceptor Blocking Drugs.

ADIS Press, 1977, Sydney;

21. Gibson, D.G.: Pharmacodynamic Properties of a-adrenoreceptor Blocking Drugs in

Man. Cardiovascular Drugs, ed. G.S. Avery, Vol. 2: β –adrenoceptor Blocking

Drugs. ADIS Press, 1977, Sydney.

22. McDevitt, D.G.: The Assessment of β-adrenoceptor Blocking Drugs in Man. Br. J.

Clin. Pharmac, 4:413, 1977.

23. Inderal Product Monograph. Ayerst Laboratories, April 1979.

24. Product Monograph, INDERAL-LA, Propranolol Hydrochloride Extended-Release

Capsules USP 60, 80, 120 and 160 mg, Pfizer Canada Inc., Date of Revision: May

20, 2016; Submission Control#: 190671

IMPORTANT: PLEASE READ

of 26

PART III: CONSUMER INFORMATION

PrAPO-PROPRANOLOL


This leaflet is part III of a three-part "Product Monograph"

published when APO-PROPRANOLOL was approved for

sale in Canada and is designed specifically for Consumers.

This leaflet is a summary and will not tell you everything

about APO-PROPRANOLOL. Contact your doctor or

pharmacist if you have any questions about the drug.

ABOUT THIS MEDICATION

What the medication is used for:

APO-PROPRANOLOL contains propranolol hydrochloride, one

of a group of substances called beta-adrenergic receptor-blocking

agents (beta blockers). It is used as:

Treatment for patients with high blood pressure;

Preventive treatment of angina pectoris (a condition

associated with sharp chest pain and difficulty breathing,

often associated with exercise);

Treatment of abnormal heart rhythms;

Prevention of migraine (severe headache often

accompanied by nausea, vomiting, and sensitivity to light);

Management of hypertrophic subaortic stenosis (a

condition associated with stress-induced chest pain,

pounding heart, and fainting);

Management of adrenal gland tumours.

What it does:

APO-PROPRANOLOL acts to reduce high blood pressure and

guard against angina pectoris.

It works by the effects it has on the heart and circulation and

also on other parts of the body.

When it should not be used:

Do not use APO-PROPRANOLOL if you:

are hypersensitive (allergic) to propranolol

hydrochloride or another beta-blocker;

are hypersensitive to any ingredient in the formulation or

component of the container. For a complete listing, see

What the important nonmedicinal ingredients are;

have had or currently have bronchial asthma or

bronchospasm (a sudden closing of muscles in the throat,

making it hard to breathe) ;

have allergic rhinitis (for example, runny nose during

the pollen season);

have a heart condition known as congestive heart failure

(a condition where the heart is unable to pump enough

blood);

have pulmonary hypertension (high blood pressure in

the arteries of the lungs, which lead to heart failure);

are prone to having hypoglycaemia (episodes of low

blood sugar);

have any of the following heart or cardiovascular

conditions:

• bradycardia (abnormally slow heart beat)

• hypotension (unusually low blood pressure)

• metabolic acidosis (when there is too much acid in

the body’s fluids)

• poor blood circulation

• sick sinus syndrome (a group of heart rhythm disorders);

• untreated phaeochromocytoma (a tumour condition in

the adrenal glands)

• uncontrolled heart failure

• Prinzmetal’s angina (a condition that produces chest

pain and pressure while at rest)

have one of the following rare hereditary diseases:

• Galactose intolerance

• Lapp lactase deficiency

• Glucose-galactose malabsorption

What the medicinal ingredient is:

Propranolol hydrochloride

What the nonmedicinal ingredients are: APO-

PROPRANOLOL contains lactose (20 mg and 120 mg),

magnesium stearate, microcrystalline cellulose, and starch

(10 mg, 40 mg and 80 mg).

For a full listing of nonmedicinal ingredients see Part 1 of the

product monograph.

What dosage forms it comes in:

10 mg tablets: Orange, round, biconvex tablet. Scored &

engraved APO over 10 on one side, other side plain. Bottles

of 100 and 1000 tablets.

20 mg tablets: Blue, hexagonal, biconvex tablet. Scored &



40 mg tablets: Green, round, biconvex tablet. Scored &



80 mg tablets: Yellow, round, biconvex tablet. Scored &



120 mg tablets: Reddish-pink, round, biconvex tablet.

Scored & engraved APO over 120 on one side, other side

plain. Bottles of 100 and 1000 tablets.

WARNINGS AND PRECAUTIONS

APO-PROPRANOLOL should never be stopped abruptly.

APO-PROPRANOLOL is not intended for emergency use. It

can be used as a starting treatment. Your doctor will tell you

how to take APO-PROPRANOLOL and will monitor your


of 26

response regularly.

If you have been taking APO-PROPRANOLOL for angina

pectoris, do not stop treatment or change the dose without

directions from your doctor.

Use caution when driving or operating machinery while taking

APO-PROPRANOLOL, as it may lead to fatigue or dizziness.

Before you use APO-PROPRANOLOL, talk to your doctor

or pharmacist if you

- have a heart condition;

- have poor circulation;

- have a history of serious allergies;

- have a history of skin reactions;

- are prone to chronic bronchitis and emphysema not

related to allergies;

- have diabetes;

- have a condition involving an over-active thyroid gland

- have or have had a severe allergic condition involving the

eyes and skin;

- have liver or kidney problems;

- are to undergo surgery;

- are pregnant or intending to become pregnant;

- are nursing;

- are taking any other medications.

APO-PROPRANOLOL is not recommended for children.

INTERACTIONS WITH THIS MEDICATION

If taken with some other medicines, the effects of APO-

PROPRANOLOL or the other medication may change. Tell

your doctor or pharmacist if you are taking or have recently

taken any other medications, including non-prescription

medicines, vitamins, minerals, natural supplements, or

alternative medicines.

Examples of drugs or substances that may interact with APO-

PROPRANOLOL include:

- Alcoholic beverages

- Diuretics (drugs used to increase urine output, such

as hydrochlorothiazide)

- Drugs used to control heart rhythm, e.g.,

disopyramide, amiodarone, propafenone, quinidine

- Warfarin (to thin the blood)

- Insulin

- Drugs used to reduce high blood pressure, e.g.,

guanethidine, clonidine, calcium channel blockers

(verapamil, diltiazem, nifedipine)

- Rizatriptan (a drug used to treat migraine headaches)

- Digitalis (a drug used to control heart rate and rhythm)

- Epinephrine (a drug used to treat severe allergic reactions)

- Cimetidine (a drug used to treat stomach ulcers and pain)

- Ergotamines (a class of drugs used to treat

migraine headaches)

- Chlorpromazine (one of a class of drugs used to

treat psychoses)

- Lidocaine (a drug used as a local anesthetic)

- Pain relief or anti-inflammatory drugs available with

or without prescriptions such as ibuprofen

- Fingolimod, a medicine used to treat multiple sclerosis

Please check with your doctor or pharmacist before taking any

other medications with APO-PROPRANOLOL.

PROPER USE OF THIS MEDICATION

Usual dose:

Take APO-PROPRANOLOL tablets exactly as directed by your doctor and your doctor will determine which dose is right for

you.

Overdose:

If you think you have taken too much APO-

PROPRANOLOL, contact your healthcare professional,

hospital emergency department or regional poison control

centre immediately, even if there are no symptoms.

Missed Dose:

If you missed a dose of this medication, take it as soon as

you remember. However, if it is almost time for your next

dose, do not take the missed dose or take a double dose to

make up for the missed tablet. Instead, go back to your

regular dosing schedule.

SIDE EFFECTS AND WHAT TO DO ABOUT THEM

Like all medicines, APO-PROPRANOLOL can cause

side effects, although not everybody gets them.

The most common side effects are abdominal pain,

nausea, vomiting, loss of appetite and diarrhea. Other side

effects include dizziness, fatigue, disturbed sleep and

nightmares, cold hands and feet, numbness and spasm in

your fingers followed by warmth and pain (Raynaud’s

phenomenon).

The most serious side effects with propranolol

hydrochloride are congestive heart failure and

bronchospasm (see When it should not be used and

WARNINGS AND PRECAUTIONS).

The following table contains a list of side effects that may

occur with APO-PROPRANOLOL. The table does not

include a complete list. Therefore, check with your

doctor immediately if you notice or are bothered by any

unusual symptoms.


of 26

SERIOUS SIDE EFFECTS, HOW OFTEN THEY HAPPEN

AND WHAT TO DO ABOUT THEM

Symptom / effect Talk with

your doctor or

pharmacist

Stop taking

drug and

call your

doctor or

pharmacist Only if

severe

In all

cases

Frequency

unknown

Allergic reactions (skin

rash, hives, itching,

swelling of the lips, face,

tongue, throat, trouble

breathing or swallowing,

wheezing, blisters of the

skin, sores or pain in the

mouth or eyes)

√

Difficulty breathing and

swollen ankles (Congestive

heart failure)

√

Abnormally low blood

pressure, dizziness

(particularly, when standing

up), tiredness

fainting

√

Bronchospasm, asthma

√

Weakness, insomnia,

headache, fatigue

√

Changes in mood,

hallucinations, memory loss

√

Dry eyes, visual

disturbances

√

Common Abdominal pain, nausea,

vomiting, diarrhea, loss of

appetite

√

Uncommon Ringing in the ears √

Low level of sugar in the

blood

(hypoglycemia)

√

This is not a complete list of side effects. For any unexpected

effects while taking APO-PROPRANOLOL, contact your

doctor or pharmacist.

HOW TO STORE IT

Store at room temperature (15oC to 30oC). Keep out of the reach

and sight of children.

Reporting Side Effects

You can report any suspected side effects associated with the use of

health products to Health Canada by:

Visiting the Web page on Adverse Reaction Reporting

(https://www.canada.ca/en/health-canada/services/drugs-

health-products/medeffect-canada/adverse-reaction-

reporting.html) for information on how to report online, by

mail or by fax; or

Calling toll-free at 1-866-234-2345.

NOTE: Contact your health professional if you need information

about how to manage your side effects. The Canada

Vigilance Program does not provide medical advice.

More Information

If you want more information about APO-PROPRANOLOL:

• Talk to your healthcare professional

• Find the full product monograph that is prepared for

healthcare professionals and includes this Consumer

Information by visiting the Health Canada website

(https://health-products.canada.ca/dpd-bdpp/index-

eng.jsp); the manufacturer’s website

(http://www.apotex.ca/products), or by calling 1-800-667-

4708.

This leaflet was prepared by: Apotex Inc., Toronto, Ontario,

M9L 1T9.

Last revised: January 29, 2021

product monograph apo-propranolol usp beta-adrenergic

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